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Biosafety assessment of delivery systems for clinical nucleic acid therapeutics

Biosafety and Health 2022年第2期4卷 105-117页

作者： Zhimin Li Li Zhang Kai Jiang Yijing Zhang Yonglin Liu Guang Hu Jie Song School of Molecular Medicine Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Institute of Basic Medicine and Cancer(IBMC) Chinese Academy of SciencesThe Cancer Hospital of the University of Chinese Academy of SciencesHangzhou 310022China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Institute of Nano Biomedicine and Engineering Department of Instrument Science and EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China School of Life Sciences Tianjin UniversityTianjin 300350China School of Biomedical Sciences Hunan UniversityChangsha 410082China

nucleic acid therapeutics,which involve transferring exogenous genes inside target cells,are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level.Ideally,this kind of treatment modality will not lead to an unwanted immune response.Compared with traditional treatment methods,nucleic acid therapeutics can achieve prolonged and stable curative effects.As an emerging treatment method,nucleic acid therapeutics have played an increasingly important role in clinical settings for the treatment of various conditions,including infectious diseases,cancer,immune-related diseases,and monogenetic diseases.To date,a large number of clinical trials have been conducted,and more than 30 nucleic acid drugs have been approved,highlighting the strong potential of this approach in clinical practice.Diverse carriers are used to protect nucleic acids from being degraded and to help them reach their targets accurately.However,some carriers are known to cause negative effects on the release and expression of nucleic acid drugs as well as adverse effects such as allergic reactions and accumulation in the liver.Therefore,biosafety assessment of delivery systems before their application in clinical settings is critical.In this review,we describe different delivery systems for nucleic acid drugs and discuss their biosafety in both preclinical and clinical studies,with particular focus on the carriers themselves,drug administration method,and overall treatment of the disease.

关键词： nucleic acid therapeutics Delivery system Biosafety Viral vector Lipid Carrier-free delivery

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Design of synthetic materials for intracellular delivery of RNAs： From siRNA-mediated gene silencing to CRISPR/Cas gene editing

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Nano Research 2018年第10期11卷 5310-5337页

作者： Jason B. Miller Daniel J. Siegwart Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center Dallas TX 75390 USA Department of Biochemistry University of Texas Southwestern Medical Center Dallas TX 75390 USA

Ribonucleic acids （RNAs） possess great therapeutic potential and can be used to treat a variety of diseases. The unique biophysical properties of RNAs, such as high molecular weight, negative charge, hydrophilicity, low stability, and potential immunogenicity, require chemical modification and development of carriers to enable intracellular delivery of RNAs for clinical use. A variety of nanornaterials have been developed for the effective in vivo delivery of short/ small RNAs, messenger RNAs, and RNAs required for gene editing technologies including clustered regularly interspaced palindromic repeat （CRISPR）/Cas. This review outlines the challenges of delivering RNA therapeutics, explores the chemical synthesis of RNA modifications and carriers, and describes the efforts to design nanomaterials that can be used for a variety of clinical indications.

关键词： nucleic acid therapeutics nanoparticles synthetic nanomaterials RNA interference （RNAi） messenger RNA （mRNA） clustered regularly inter-spaced palindromic repeat（CRISPR）/Cas

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Application of cationic liposomes for delivery of nucleic acids

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Asian Journal of Pharmaceutical Sciences 2013年第2期8卷 72-80页

作者： Gayong Shim Mi-Gyeong Kim Joo Yeon Park Yu-Kyoung Oh College of Pharmacy Seoul National UniversityDaehak-dongSeoul 151-742South Korea

nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposomes have been studied as a means to enhance thestability of nucleic acid therapeutics in the bloodstream and improve their cellular delivery.As nucleic acid therapeutics, siRNA and plasmid DNA have been extensively tested fordelivery using cationic liposomes. This review discusses recent progress in the applicationof cationic liposomes for the delivery of nucleic acid therapeutics.

关键词： Cationic lipid Liposomes Delivery nucleic acid therapeutics siRNA Plasmid DNA

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